DESCRIPTION: The long term goal of these studies is to understand the structure and function of the von Willebrand receptor GP Ib at a molecular level. This receptor consists of 4 subunits, GP Ib alpha, GP Ib beta, GP IX, and GP V. Shear forces affect the interaction between GP Ib and von Willebrand factor and the first specific aim is to determine whether shear affects GP Ib, von Willebrand factor, or both. Experiments in this specific aim will also characterize the binding domains involved in the shear-induced binding of soluble and immobilized von Willebrand factor to GP Ib. The GP Ib-von Willebrand factor interaction leads to intracellular changes and the second specific aim is to determine how the intracellular domains of the GP Ib complex participate in this transmembrane signaling. The role of GP Ib beta phosphorylation, protein 14-3-3, and actin-binding protein in this signaling will be assessed.